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Stopping Tyrosine Kinase Inhibitors in Affecting Treatment-Free Remission in Patients with Chronic Phase Chronic Myeloid Leukemia

Trial Status: Active

This phase II trial studies how stopping tyrosine kinase inhibitors will affect treatment-free remission in patients with chronic myeloid leukemia in chronic phase. When the level of disease is very low, it's called molecular remission. TKIs are a type of medication that help keep this level low. However, after being in molecular remission for a specific amount of time, it may not be necessary to take tyrosine kinase inhibitors. It is not yet known whether stopping tyrosine kinase inhibitors will help patients with chronic myeloid leukemia in chronic phase continue or re-achieve molecular remission.

Inclusion Criteria

  • Patient must have been diagnosed with CML-CP at < 18 years of age.
  • Patient must have histologic verification of CML-CP at original diagnosis
  • Patient must be in molecular remission (MR) with a BCR-ABL1 level of =< 0.01% BCR-ABL1 as measured using the International Scale (IS) by RQ-PCR for >= 2 consecutive years at the time of enrollment * Please note: The lab evaluating disease status and molecular response for this study must be College of American Pathology (CAP) and/or Clinical Laboratory Improvement Amendments (CLIA) certified (United States [US] only), sites in other countries must be certified by their accredited authorities. All labs must use the International Scale guidelines with a sensitivity of detection assay =< 0.01% BCR-ABL1 and be able to report results in =< 2 weeks
  • Patient must have received any TKI for a minimum of 3 consecutive years at time of enrollment
  • Patient agrees to discontinue TKI therapy
  • REGULATORY REQUIREMENTS
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
  • ELIGIBILITY FOR PATIENT-REPORTED OUTCOMES (PROs):
  • Age >= 8 years at the time of enrollment
  • Ability to understand English or Spanish
  • Cognitive ability to complete instruments according to the primary team
  • ELIGIBILITY FOR AAML18P1 NEUROCOGNITIVE STUDY:
  • Patient must be 5 years or older at the time of enrollment
  • English-, French- or Spanish-speaking
  • No known history of neurodevelopmental disorder prior to diagnosis of CML (e.g., Down syndrome, Fragile X, William syndrome, mental retardation)
  • No significant visual or motor impairment that would prevent computer use or recognition of visual test stimuli

Exclusion Criteria

  • Known T3151 mutation
  • Additional clonal chromosomal abnormalities in Philadelphia chromosome (Ph) positive (+) cells at any time prior to enrollment that include “major route” abnormalities (second Ph, trisomy 8, isochromosome 17q, trisomy 19), complex karyotype or abnormalities of 3q26.2
  • History of accelerated phase or blast crisis CML
  • Female patients who are pregnant
  • Lactating females are not eligible unless they have agreed not to breastfeed their infants
  • Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained

Alabama

Birmingham
Children's Hospital of Alabama
Status: ACTIVE
Contact: Site Public Contact
Phone: 205-638-9285

Arkansas

Little Rock
Arkansas Children's Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 501-364-7373

California

Downey
Kaiser Permanente Downey Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 626-564-3455
Madera
Valley Children's Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 559-353-3000
Oakland
Kaiser Permanente-Oakland
Status: ACTIVE
Contact: Site Public Contact
Phone: 877-642-4691
Email: Kpoct@kp.org

Colorado

Aurora
Children's Hospital Colorado
Status: ACTIVE
Contact: Site Public Contact
Phone: 303-764-5056
Denver
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 303-839-6000

Delaware

Wilmington
Alfred I duPont Hospital for Children
Status: ACTIVE
Contact: Site Public Contact
Phone: 302-651-6884

Florida

Fort Myers
Golisano Children's Hospital of Southwest Florida
Status: ACTIVE
Contact: Site Public Contact
Phone: 239-343-5333
Jacksonville
Nemours Children's Clinic-Jacksonville
Status: ACTIVE
Contact: Site Public Contact
Phone: 904-697-3529
Miami
Nicklaus Children's Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 888-624-2778
University of Miami Miller School of Medicine-Sylvester Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 305-243-2647
Orlando
Nemours Children's Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 407-650-7715

Georgia

Atlanta
Children's Healthcare of Atlanta - Egleston
Status: ACTIVE
Contact: Site Public Contact
Phone: 404-785-2025

Illinois

Chicago
Lurie Children's Hospital-Chicago
Status: ACTIVE
Contact: Site Public Contact
Phone: 773-880-4562
Peoria
Saint Jude Midwest Affiliate
Status: ACTIVE
Contact: Site Public Contact
Phone: 888-226-4343

Indiana

Indianapolis
Riley Hospital for Children
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-248-1199

Kentucky

Lexington
University of Kentucky / Markey Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 859-257-3379
Louisville
Norton Children's Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 502-629-5500

Maryland

Baltimore
Sinai Hospital of Baltimore
Status: ACTIVE
Contact: Site Public Contact
Phone: 410-601-6120
Bethesda
Walter Reed National Military Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 301-319-2100

Massachusetts

Boston
Dana-Farber Cancer Institute
Status: ACTIVE
Contact: Site Public Contact
Phone: 877-442-3324

Michigan

Ann Arbor
C S Mott Children's Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-865-1125
Detroit
Wayne State University / Karmanos Cancer Institute
Status: ACTIVE
Contact: Site Public Contact
Phone: 313-576-9790

Minnesota

Minneapolis
Children's Hospitals and Clinics of Minnesota - Minneapolis
Status: ACTIVE
Contact: Site Public Contact
Phone: 612-813-5193

Mississippi

Jackson
University of Mississippi Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 601-815-6700

Missouri

Columbia
Columbia Regional
Status: ACTIVE
Contact: Site Public Contact
Kansas City
Children's Mercy Hospitals and Clinics
Status: ACTIVE
Contact: Site Public Contact
Phone: 816-302-6808
Email: rryan@cmh.edu

Nebraska

Omaha
Children's Hospital and Medical Center of Omaha
Status: ACTIVE
Contact: Site Public Contact
Phone: 402-955-3949
University of Nebraska Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 402-559-6941

New Jersey

Hackensack
Hackensack University Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 201-996-2879
New Brunswick
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 732-235-8675
Paterson
Saint Joseph's Regional Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 973-754-2207

New York

Mineola
NYU Winthrop Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 646-754-4624
New York
Memorial Sloan Kettering Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 212-639-7592
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 212-305-6361
Rochester
University of Rochester
Status: ACTIVE
Contact: Site Public Contact
Phone: 585-275-5830

North Carolina

Chapel Hill
UNC Lineberger Comprehensive Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 877-668-0683
Charlotte
Carolinas Medical Center / Levine Cancer Institute
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-804-9376
Winston-Salem
Wake Forest University Health Sciences
Status: ACTIVE
Contact: Site Public Contact
Phone: 336-713-6771

Ohio

Akron
Children's Hospital Medical Center of Akron
Status: ACTIVE
Contact: Site Public Contact
Phone: 330-543-3193
Columbus
Nationwide Children's Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 614-072-2657

Oklahoma

Oklahoma City
University of Oklahoma Health Sciences Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 405-271-8777

Pennsylvania

Hershey
Penn State Children's Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 717-531-6012
Philadelphia
Children's Hospital of Philadelphia
Status: ACTIVE
Contact: Site Public Contact
Phone: 267-425-5544
Pittsburgh
Children's Hospital of Pittsburgh of UPMC
Status: ACTIVE
Contact: Site Public Contact
Phone: 412-692-8570

Rhode Island

Providence
Rhode Island Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 401-444-1488

South Dakota

Sioux Falls
Sanford USD Medical Center - Sioux Falls
Status: ACTIVE
Contact: Site Public Contact
Phone: 605-312-3320

Tennessee

Knoxville
East Tennessee Childrens Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 865-541-8266
Memphis
Saint Jude Children's Research Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 888-226-4343

Texas

Dallas
Medical City Dallas Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 972-566-5588
UT Southwestern / Simmons Cancer Center-Dallas
Status: ACTIVE
Contact: Site Public Contact
Phone: 214-648-7097
San Antonio
Children's Hospital of San Antonio
Status: ACTIVE
Contact: Site Public Contact

Utah

Salt Lake City
Primary Children's Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 801-585-5270

Virginia

Norfolk
Children's Hospital of The King's Daughters
Status: ACTIVE
Contact: Site Public Contact
Phone: 757-668-7243
Richmond
Virginia Commonwealth University / Massey Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 804-628-1914

Washington

Seattle
Seattle Children's Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 866-987-2000
Spokane
Providence Sacred Heart Medical Center and Children's Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-228-6618
Tacoma
Mary Bridge Children's Hospital and Health Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 253-403-1461

Wisconsin

Madison
University of Wisconsin Hospital and Clinics
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-622-8922

Manitoba

Winnipeg
CancerCare Manitoba
Status: ACTIVE
Contact: Site Public Contact
Phone: 866-561-1026

Nova Scotia

Halifax
IWK Health Centre
Status: ACTIVE
Contact: Site Public Contact
Phone: 902-470-8037

Ontario

Hamilton
McMaster Children's Hospital at Hamilton Health Sciences
Status: ACTIVE
Contact: Site Public Contact
Phone: 905-521-2100
Ottawa
Children's Hospital of Eastern Ontario
Status: ACTIVE
Contact: Site Public Contact
Phone: 613-738-3931
Toronto
Hospital for Sick Children
Status: ACTIVE
Contact: Site Public Contact
Phone: 416-813-7654

Quebec

Montreal
Centre Hospitalier Universitaire Sainte-Justine
Status: ACTIVE
Contact: Site Public Contact
Phone: 514-345-4931
The Montreal Children's Hospital of the MUHC
Status: ACTIVE
Contact: Site Public Contact
Phone: 514-412-4445
Quebec
Centre Hospitalier Universitaire de Quebec
Status: ACTIVE
Contact: Site Public Contact
Phone: 418-525-4444

Australia

Clayton
Monash Medical Center-Clayton Campus
Status: ACTIVE
Contact: Site Public Contact
Phone: (03) 9928 8111
Perth
Perth Children's Hospital
Status: ACTIVE
Contact: Site Public Contact
Westmead
The Children's Hospital at Westmead
Status: ACTIVE
Contact: Site Public Contact
Phone: 61-2-9845 1400

PRIMARY OBJECTIVES:

I. To determine the 2-year treatment free remission (TFR) rate of children, adolescents, and young adults with chronic myeloid leukemia - chronic phase (CML-CP) following discontinuation tyrosine kinase inhibitor (TKI).

II. To estimate the re-induction rate and maintenance of molecular remission (BCR-ABL1 =< 0.1%) at 1 year after restarting TKI for children, adolescents, and young adults.

SECONDARY OBJECTIVE:

I. To describe clinical factors and laboratory correlates affecting the persistence of major molecular remission (MMR) and re-initiation of treatment after stopping TKI (e.g. patient demographics, duration and level of prior molecular remission, duration and type of TKI, clinical presentation at diagnosis and immune studies).

EXPLORATORY OBJECTIVES:

I. To describe change in height standard deviation score over time in patients who are able to discontinue their TKI.

II. To describe the long-term health outcomes including but not limited to gonadal function, endocrine function, and bone metabolism in patients who are able to discontinue TKI as well as those that need to restart TKIs.

III. To describe differences in patient-reported health status after stopping TKIs, including those who need to resume TKI after stopping.

IV. To describe the incidence and characteristics of TKI withdrawal syndrome in children.

V. To evaluate changes in neurocognitive outcomes of patients enrolled on this study using a patient-completed, performance-based, computerized measure of neuropsychological functioning and a parent-report/self-report questionnaire.

OUTLINE:

Patients stop taking TKI medication within 10 days after enrollment. Patients undergo peripheral blood collection to monitor loss of MMR every 4 weeks in year 1, every 6 weeks in year 2, and every 12 weeks in year 3. Patients who lose their molecular remission may restart TKI medication and are monitored every 4 weeks in year 1, every 6 weeks in year 2, and every 12 weeks in year 3.

After completion of study treatment, patients are followed up annually.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Children's Oncology Group

Principal Investigator
Sonali Chaudhury

  • Primary ID AAML18P1
  • Secondary IDs NCI-2018-03439
  • Clinicaltrials.gov ID NCT03817398